-
International Journal of Dermatology Mar 2024Exposure to solar ultraviolet radiation (UVR) is associated with several cutaneous adverse effects. However, to the best of our knowledge, in South Africa there are no... (Review)
Review
Exposure to solar ultraviolet radiation (UVR) is associated with several cutaneous adverse effects. However, to the best of our knowledge, in South Africa there are no formal guidelines on sun protection. A group of South African dermatologists and researchers convened over the course of 1 year to deliberate on integrated advice for sun protection among the multi-ethnic South African population. For people with light skin and those with genetic skin disorders (e.g., oculocutaneous albinism), sun protection was identified as critical to prevent sunburn, skin cancer, and photoaging. The evidence is less clear for people with medium and darker skin types, especially the latter, in whom melanin may confer a degree of protection against some parts of the solar spectrum. Recent studies have demonstrated that visible light can cause pigmentary changes in individuals with darker skin types in particular. Sun protection for people of all skin colors is beneficial to protect against photoaging and ocular damage. Herein sun protection advice is suggested for South Africans of all skin colors to reduce morbidity and mortality from sun exposure, particularly relating to skin cancer. Several knowledge gaps are identified as future research priorities.
Topics: Humans; Ultraviolet Rays; South Africa; Sunlight; Sunburn; Skin Neoplasms; Sunscreening Agents
PubMed: 38124402
DOI: 10.1111/ijd.16980 -
Investigative Ophthalmology & Visual... Jun 2022We investigated axial length (AL) distributions in inherited retinal diseases (IRDs), comparing them with reference cohorts.
PURPOSE
We investigated axial length (AL) distributions in inherited retinal diseases (IRDs), comparing them with reference cohorts.
METHODS
AL measurements from IRD natural history study participants were included and compared with reference cohorts (TwinsUK, Raine Study Gen2-20, and published studies). Comparing with the Raine Study cohort, formal odds ratios (ORs) for AL ≥ 26 mm or AL ≤ 22 mm were derived for each IRD (Firth's logistic regression model, adjusted for age and sex).
RESULTS
Measurements were available for 435 patients (median age, 19.5 years). Of 19 diseases, 10 had >10 participants: ABCA4 retinopathy; CNGB3- and CNGA3-associated achromatopsia; RPGR-associated disease; RPE65-associated disease; blue cone monochromacy (BCM); Bornholm eye disease (BED); TYR- and OCA2-associated oculocutaneous albinism; and GPR143-associated ocular albinism. Compared with the TwinsUK cohort (n = 322; median age, 65.1 years) and Raine Study cohort (n = 1335; median age, 19.9 years), AL distributions were wider in the IRD groups. Increased odds for longer ALs were observed for BCM, BED, RPGR, RPE65, OCA2, and TYR; increased odds for short AL were observed for RPE65, TYR, and GPR143. In subanalysis of RPGR-associated disease, longer average ALs occurred in cone-rod dystrophy (n = 5) than rod-cone dystrophy (P = 0.002).
CONCLUSIONS
Several diseases showed increased odds for longer AL (highest OR with BCM); some showed increased odds for shorter AL (highest OR with GPR143). Patients with RPE65- and TYR-associated disease showed increased odds for longer and for shorter eyes. Albinism genes were associated with different effects on AL. These findings add to the phenotype of IRDs and may yield insights into mechanisms of refractive error development.
Topics: ATP-Binding Cassette Transporters; Albinism, Oculocutaneous; Eye Proteins; Genetic Diseases, X-Linked; Humans; Mutation; Myopia; Retina; Retinal Diseases
PubMed: 35704304
DOI: 10.1167/iovs.63.6.15 -
Genetics in Medicine : Official Journal... Mar 2021Albinism is a clinically and genetically heterogeneous condition. Despite analysis of the 20 known genes, ~30% patients remain unsolved. We aimed to identify new genes...
PURPOSE
Albinism is a clinically and genetically heterogeneous condition. Despite analysis of the 20 known genes, ~30% patients remain unsolved. We aimed to identify new genes involved in albinism.
METHODS
We sequenced a panel of genes with known or predicted involvement in melanogenesis in 230 unsolved albinism patients.
RESULTS
We identified variants in the Dopachrome tautomerase (DCT) gene in two patients. One was compound heterozygous for a 14-bp deletion in exon 9 and c.118T>A p.(Cys40Ser). The second was homozygous for c.183C>G p.(Cys61Trp). Both patients had mild hair and skin hypopigmentation, and classical ocular features. CRISPR-Cas9 was used in C57BL/6J mice to create mutations identical to the missense variants carried by the patients, along with one loss-of-function indel. When bred to homozygosity the three mutations revealed hypopigmentation of the coat, milder for Cys40Ser compared with Cys61Trp or the frameshift mutation. Histological analysis identified significant hypopigmentation of the retinal pigmented epithelium (RPE) indicating that defective RPE melanogenesis could be associated with eye and vision defects. DCT loss of function in zebrafish embryos elicited hypopigmentation both in melanophores and RPE cells.
CONCLUSION
DCT is the gene for a new type of oculocutaneous albinism that we propose to name OCA8.
Topics: Albinism, Oculocutaneous; Animals; Humans; Intramolecular Oxidoreductases; Mice; Mice, Inbred C57BL; Mutation; Zebrafish
PubMed: 33100333
DOI: 10.1038/s41436-020-00997-8 -
Genes Jan 2023The diagnostic yield of genetic testing for ocular/oculocutaneous albinism (OA/OCA) in a diverse pediatric population in the United States (U.S.) is unclear. Phenotypes...
The diagnostic yield of genetic testing for ocular/oculocutaneous albinism (OA/OCA) in a diverse pediatric population in the United States (U.S.) is unclear. Phenotypes of 53 patients who presented between 2006-2022 with OA/OCA were retrospectively correlated with genetic testing results. Genetic diagnostic yield was defined as detection of pathogenic/likely pathogenic variant(s) matching the anticipated inheritance for that gene-disease relationship. Variant reclassifications of those with variants of uncertain significance (VUS) and without positive diagnostic yield were completed. Overall initial genetic diagnostic yield of OA/OCA was 66%. There was no significant difference ( = 0.59) between race and ethnicities (Black (78%), White (59%), Hispanic/Latino (64%)); however, the diagnostic yield of OA (33%) was significantly lower ( = 0.007) than OCA (76%). Causative variants in (28%) and (20%) were most common. Further, Hermansky-Pudlak syndrome variants were identified in 9% of patients. Re-classification of VUS in non-diagnostic cases resulted in genetic diagnoses for 29% of individuals and increased overall diagnostic yield to 70% of all subjects. There is a high diagnostic yield of genetic testing of patients overall with OA/OCA in a diverse U.S. based pediatric population. Presence or absence of cutaneous involvement of albinism significantly affects genetic diagnostic yield.
Topics: Child; Humans; Retrospective Studies; Mutation; Membrane Transport Proteins; Genetic Testing; Albinism, Ocular; Hermanski-Pudlak Syndrome
PubMed: 36672876
DOI: 10.3390/genes14010135 -
Ophthalmic Genetics Dec 2022Albinism is a group of genetic disorders characterized by general skin and retinal hypopigmentation. It is in most cases an autosomal recessive condition. Foveal...
BACKGROUND
Albinism is a group of genetic disorders characterized by general skin and retinal hypopigmentation. It is in most cases an autosomal recessive condition. Foveal hypoplasia (FH) is one of the main criteria for the diagnosis of albinism. The aim of this study was to analyze the macular profile of the parents of patients with albinism.
METHODS
This study included a case series of 27 patients with albinism seen in Rothschild Foundation between April 2017 and February 2020. Spectral-domain optical coherence tomography (SD-OCT) and OCT angiography (OCT-A) were performed in every patient when possible and in every available parents. FH was graded according to Thomas' classification based on OCT. Next generation sequencing-based gene panel testing was performed in parents and children when a FH was detected on OCT in a parent.
RESULTS
Twenty-seven patients with albinism were examined. Nine parents had FH based on the OCT B-scan (33%). In parents without FH based on the SD-OCT B-scan (67%), OCT-A showed a reduced avascular zone in the deep vascular plexus in 4 parents. Six parents carried variants that could explain their phenotype, including TYR R402Q hypomorphic alleles.
CONCLUSION
This study showed the presence of FH in parents of patients with albinism, and aimed to genetically explain this phenotype.
Topics: Humans; Fovea Centralis; Retina; Albinism; Albinism, Oculocutaneous; Albinism, Ocular; Vision Disorders; Tomography, Optical Coherence
PubMed: 36098180
DOI: 10.1080/13816810.2022.2121841 -
The British Journal of Ophthalmology May 2016The classic form of Chédiak-Higashi syndrome (CHS), an autosomal recessive disorder of lysosomal trafficking with childhood onset caused by mutations in ITALIC! LYST,...
BACKGROUND
The classic form of Chédiak-Higashi syndrome (CHS), an autosomal recessive disorder of lysosomal trafficking with childhood onset caused by mutations in ITALIC! LYST, is typified ophthalmologically by ocular albinism with vision loss attributed to foveal hypoplasia or nystagmus. Optic nerve involvement and ophthalmological manifestations of the late-onset neurodegenerative form of CHS are rarely reported and poorly detailed.
METHODS
Case series detailing ophthalmological and neurological findings in three adult siblings with the late-onset form of CHS.
RESULTS
All three affected siblings lacked features of ocular albinism and demonstrated significant optic nerve involvement as evidenced by loss of colour and contrast vision, central visual field loss, optic nerve pallor, retinal nerve fibre layer thinning by optical coherence tomography (OCT) and abnormal visual evoked potential, with severity corresponding linearly to age of the sibling and severity of neurological disease. Further, unusual prominence of a 'third line' on macular OCT that may be due to abnormal melanosomes was seen in all three siblings and in their father. Neurological involvement included parkinsonism, cerebellar ataxia and spastic paraparesis.
CONCLUSIONS
This report expands the ophthalmological phenotype of the late-onset neurodegenerative form of CHS to include optic neuropathy with progressive vision loss, even in the absence of ocular albinism, and abnormal prominence of the interdigitation zone between cone outer segment tips and apical processes of retinal pigment epithelium cells on macular OCT.
Topics: Adult; Chediak-Higashi Syndrome; Evoked Potentials, Visual; Female; Humans; Male; Optic Nerve Diseases; Phenotype; Siblings; Tomography, Optical Coherence; Vision Disorders; Visual Acuity; Visual Fields
PubMed: 26307451
DOI: 10.1136/bjophthalmol-2015-307012 -
International Journal of Molecular... Sep 2016To investigate whether () is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in...
To investigate whether () is differentially expressed in the skin of mice with different coat colors and to determine its correlation with coat color establishment in mouse, the expression patterns and tissue distribution characterization of in the skin of mice with different coat colors were qualitatively and quantitatively analyzed by real-time quantitative PCR (qRT-PCR), immunofluorescence staining and Western blot. The qRT-PCR analysis revealed that mRNA was expressed in all mice skin samples tested, with the highest expression level in brown skin, a moderate expression level in black skin and the lowest expression level in gray skin. Positive OA1 protein bands were also detected in all skin samples by Western blot analysis. The relative expression levels of OA1 protein in both black and brown skin were significantly higher than that in gray skin, but there was no significant difference between black and brown mice. Immunofluorescence assays revealed that OA1 was mainly expressed in the hair follicle matrix, the inner and outer root sheath in the skin tissues with different coat colors. To get further insight into the important role of in the melanocytes' pigmentation, we transfected the into mouse melanocytes and then detected the relative expression levels of pigmentation-related gene. Simultaneously, we tested the melanin content of melanocytes. As a result, the overexpression of significantly increased the expression levels of (), (), () and (). However, the () level was attenuated. By contrast, the level of () was unaffected by overexpression. Furthermore, we observed a significant increase in melanin content in mouse melanocyte transfected . Therefore, we propose that may participate in the formation of coat color by regulating the level of and the number, size, motility and maturation of melanosome.
PubMed: 27690000
DOI: 10.3390/ijms17101596 -
Fish Physiology and Biochemistry Apr 2021Paralichthys olivaceus is the kind of cold-water benthic marine fish. In the early stages of development, the symmetrical juveniles transform into an asymmetrical body...
Single-nucleotide polymorphisms responsible for pseudo-albinism and hypermelanosis in Japanese flounder (Paralichthys olivaceus) and reveal two genes related to malpigmentation.
Paralichthys olivaceus is the kind of cold-water benthic marine fish. In the early stages of development, the symmetrical juveniles transform into an asymmetrical body shape through metamorphosis for adapting benthic life. After that, one side of the fish body is attached to the ground, and the eyes turn to the opposite side which is called ocular side. The body color also appears asymmetry. The skin on the ocular side is dark brown, and the skin on the blind side is white without pigmentation. Pseudo-albinism and hypermelanosis have been considered distinct body color disorders in flatfish. Pseudo-albinism and hypermelanosis in Paralichthys olivaceus are due to abnormal or uneven pigment distribution, due to the interaction of hereditary and environmental factors, rather than a single-nucleotide mutation of a specific gene. Here, we report three single-nucleotide polymorphisms (SNPs) responsible for both pseudo-albinism and hypermelanosis, which are located on two body color-related genes involved in melanogenesis-related pathways. c.2440C>A (P. V605I) and c.2271-96T>C are located on the Inositol 1,4,5-trisphosphate receptor type 2-like (ITPR2) (Gene ID: 109624047), they are located in exon 16 and the non-coding region, respectively, and c.2406C>A (P.H798N) is located in exon 13 of the adenylate cyclase type 6-like (AC6) gene(Gene ID: 109630770). ITPR2 and AC6 expression, which both participate in the thyroid hormone synthesis pathway associated with pseudo-albinism and hypermelanosis in P. olivaceus, were also investigated using qRT-PCR. In hypermelanotic fish, there were relatively higher levels of expression in ITPR2 and AC6 mRNA of hyper-pigmented skin of blind side than that of non-pigmented skin on the blind side and pigmented skin on the ocular side, while in pseudo-albino fish, expression level of ITPR2 and AC6 mRNA in pigmented skin of ocular side was significantly higher than that in non-pigmented skin both ocular and blind side. The results indicated that the expression of the two genes in abnormal parts of body color is positively correlated with pigmentation, suggesting that the influence of abnormal expression of two genes on the pigmentation in abnormal parts of body color deserves further study.
Topics: Adenylyl Cyclases; Animals; Fish Proteins; Flounder; Genotype; Inositol 1,4,5-Trisphosphate Receptors; Polymorphism, Single Nucleotide; Skin Pigmentation
PubMed: 33405062
DOI: 10.1007/s10695-020-00916-3 -
The European Journal of Neuroscience Apr 2019In albinism of all species, perturbed melanin biosynthesis in the eye leads to foveal hypoplasia, retinal ganglion cell misrouting, and, consequently, altered binocular... (Review)
Review
In albinism of all species, perturbed melanin biosynthesis in the eye leads to foveal hypoplasia, retinal ganglion cell misrouting, and, consequently, altered binocular vision. Here, written before he died, Ray Guillery chronicles his discovery of the aberrant circuitry from eye to brain in the Siamese cat. Ray's characterization of visual pathway anomalies in this temperature sensitive mutation of tyrosinase and thus melanin synthesis in domestic cats opened the exploration of albinism and simultaneously, a genetic approach to the organization of neural circuitry. I follow this account with a remembrance of Ray's influence on my work. Beginning with my postdoc research with Ray on the cat visual pathway, through my own work on the mechanisms of retinal axon guidance in the developing mouse, Ray and I had a continuous and rich dialogue about the albino visual pathway. I will present the questions Ray posed and clues we have to date on the still-elusive link between eye pigment and the proper balance of ipsilateral and contralateral retinal ganglion cell projections to the brain.
Topics: Albinism, Ocular; Animals; Cats; Genetics; History, 20th Century; History, 21st Century; Mice; Monophenol Monooxygenase; Neurosciences; Retina; Visual Pathways
PubMed: 30801828
DOI: 10.1111/ejn.14396 -
Case Reports in Ophthalmological... 2015Introduction. Laurence-Moon-Biedl (LMB) syndrome is a rare autosomal-recessive ciliopathy with manifold symptomatology. The cardinal clinical features include retinitis...
Introduction. Laurence-Moon-Biedl (LMB) syndrome is a rare autosomal-recessive ciliopathy with manifold symptomatology. The cardinal clinical features include retinitis pigmentosa, obesity, intellectual delay, polydactyly/syndactyly, and hypogenitalism. In this paper, the authors report on three siblings with Laurence-Moon-Biedl syndrome associated with a probable pseudocycloid form of congenital nystagmus. Methods. This was a case study conducted at King Khaled Hospital. Results. The authors assert that the nystagmus in Laurence-Moon-Biedl syndrome is essentially similar to idiopathic motor-defect nystagmus and the nystagmus seen in optic nerve hypoplasia, ocular albinism, and bilateral opacities of the ocular media. Conclusion. The data support the previous hypothesis that there is a common brain stem motor abnormality in sensory-defect and motor-defect nystagmus.
PubMed: 25984376
DOI: 10.1155/2015/439409